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Repulsive Apoptosis During Exposure of Mesencephalic Neural Stem Cells to Silver Nanoparticles in a Neurosphere Assay In Vitro

[ Vol. 12 , Issue. 1 ]


Masami Ishido, Eiko Shimaya, Rumiko Usu, Yoshika Kurokawa and Seishiro Hirano   Pages 43 - 51 ( 9 )


Neurodevelopmental toxicity of silver nanoparticles (AgNPs) remains largely unknown. In this study, we applied a neurosphere assay for neurodevelopmental effects of AgNPs. The neural stem cells were isolated from rat mesencephalon. They were cultured as a sphere. In an assay with coated plates, cells appeared by anchoraging on the dish and then started to migrate along the radial axis from the neurosphere. AgNPs inhibited cell migration in a dose-dependent manner. There was a linear correlation between the inhibition of migration and the logarithm of the particle concentration (1.25–10 μg/ml); the half-maximal inhibitory concentration was 0.41 μg/ml for 16-h exposure. Preceding migrated cells were retarded and/or collapsed by exposure to AgNPs: lower doses of AgNPs (0.31–1.2 μg/ml) caused a 42% retardation for 48 h, while higher doses of AgNPs (2.5–10 μg/ml) collasped migrating cells. Furthermore, collapsed cells were TUNEL-positive and showed a defect in the mitochondrial membrane potential. Thus, we showed the neurodevelopmental toxicity of AgNPs using an in vitro neurosphere assay system.


Apoptosis, migration, neural stem cell, neurosphere, repulsion, silver nanoparticle.


Center for Environmental Risk Research, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.

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